What is Kernicterus?
Kernicterus, or “bilirubin encephalopathy”, is a kind of brain damage caused by a natural substance called bilirubin, and it’s often seen in babies. Bilirubin is a waste product removed from the body by the liver — it’s what gives bruises and urine their yellow color. But when there’s an issue causing the body to create too much bilirubin or preventing the liver from removing it, bilirubin levels in the blood can rise above 25 mg/dL.
There are two types of bilirubin: indirect (unconjugated) and direct (conjugated). The indirect form is fat-soluble, meaning it can flow through fat particles, allowing it to cross a protective barrier from the blood into the brain. On the other hand, the direct form is water-soluble, so it can’t cross this barrier.
When indirect bilirubin enters the brain, it gets stuck in a particular place in the brain called the basal ganglia. The exposure to this high level of bilirubin can then lead to different types of brain-related problems or nervous system effects, which are referred to as “neurologic sequelae”.
What Causes Kernicterus?
Unconjugated hyperbilirubinemia is a condition characterized by high levels of a yellow substance called bilirubin in the blood. This could be due to the body producing too much bilirubin or the body not being able to get rid of it properly.
Bilirubin could increase due to a few reasons:
1. Polycythemia: Having too many red blood cells can increase their turnover rate, leading to more bilirubin.
2. Hemolysis: This is a process where red blood cells are destroyed. Conditions like erythroblastosis fetalis, and newborn hemolytic disease, or abnormalities in the red blood cells could cause this.
3. Birth Injuries: Certain injuries at birth, including cephalohematoma (a bleeding underneath the scalp), subgaleal hemorrhage (bleeding under the scalp), or bruises from birth trauma can lead to an increase in bilirubin.
On the other hand, you may have trouble removing bilirubin from your system because:
1. Hypoalbuminemia: Bilirubin is usually connected to a protein called albumin. If there’s less albumin, more bilirubin remains unattached or “free” in your system.
2. Hereditary Bilirubin Conjugation Defects: If you have Crigler-Najjar syndrome or Gilbert syndrome, it means your body lacks the enzyme (called UDGPT) for turning bilirubin into a form your body can get rid of.
3. Problems in your bile system: The bile system helps with processing and removing bilirubin.
4. Breast Milk Jaundice: An enzyme in breast milk can turn bilirubin back to its unprocessed form.
Based on data from a register for kernicterus, a severe form of jaundice, in the United States, over half of the cases had conditions known to raise bilirubin levels. Conditions that affect red blood cells were common, as were birth injuries, but for almost half the infants, no underlying explanation could be identified.
Risk Factors and Frequency for Kernicterus
Kernicterus, a condition most often found in kids, primarily affects African Americans and South Asians and is slightly more prevalent in boys than girls. The exact cases of kernicterus in the United States remain unknown. When it comes to bilirubin—a substance that can cause kernicterus—production, Asian, Hispanic, Native American, and Eskimo infants produce more than white infants, while Black infants produce less. Premature babies face a higher risk of developing kernicterus than full-term babies.
- Kernicterus is more common in African American and South Asian children, and slightly more in boys than girls.
- The number of cases in the United States is unknown.
- Asian, Hispanic, Native American, and Eskimo infants produce more bilirubin, which can lead to kernicterus, than white infants.
- Black infants produce less bilirubin than white infants.
- Premature babies have a higher risk of developing kernicterus than full-term babies.
- Baby boys have higher levels of bilirubin than baby girls.
- For babies with bilirubin levels over 30 mg/dL, 1 in 7 risks chronic kernicterus.
- Kernicterus can also happen in babies with bilirubin levels under 25 mg/dL, but the risk for the population is unknown.
Signs and Symptoms of Kernicterus
Kernicterus patients show different symptoms according to their age and overall health condition. To make an accurate diagnosis, doctors need to gather a thorough patient history. This includes the onset and duration of jaundice, family medical history, lifestyle habits of the mother like drug or alcohol use, and any pre-existing conditions in the mother.
Additionally, the birth history and postnatal history of babies can provide clues toward diagnosing kernicterus. Often, physical symptoms like injuries after birth or manifestations of bleeding can contribute to this condition.
Physical examinations, specifically neurological assessments, are crucial for diagnosing kernicterus. Examining the baby’s level of consciousness, heart rate, breathing, and oxygen saturation are important initial steps. Furthermore, checking the baby’s fontanelles for any increase in intracranial pressure can also be revealing.
Neurological abnormalities associated with high bilirubin levels in the blood are clubbed under the term Bilirubin-Induced Neurologic Dysfunction (BIND), which can be classified as acute and chronic:
- Acute bilirubin encephalopathy, which can be further broken down into three phases:
- Stage one: Weakness, lethargy, and poor feeding
- Stage two: Extensor hypertonia, backward stretching of the neck, severe arching of the back
- Stage three: Lower than normal muscle tone, typically seen in infants older than one week
- Chronic bilirubin encephalopathy, which progresses slowly and can include:
- Lower than normal muscle tone
- Overactive reflexes
- Delayed achievement of developmental milestones
- Visual and hearing defects
- Involuntary and uncontrolled movement patterns (choreoathetoid cerebral palsy)
Finally, an abdominal examination might show signs of an enlarged liver or spleen, which can indicate a blood disorder that causes destruction of red blood cells.
Testing for Kernicterus
When diagnosing and treating kernicterus, a number of different tests and examinations are run. These include:
Blood tests –
These are the most important aspects to look into. Tests to measure total and direct bilirubin can help track the disease’s progression. Bilirubin is a substance that the body produces when replacing old blood cells. If bilirubin levels are too high, this can indicate kernicterus.
Testing the blood type of both the mother and infant can help check for a condition called Rh incompatibility. Treatment with a medication known as Rho(D) immune globulin can prevent a severe outcome of this condition called erythroblastosis fetalis, which can lead to very high bilirubin levels.
Looking at the reticulocyte count is also helpful. Reticulocytes are immature red blood cells, and their count can indicate if there is ongoing break down of red blood cells, anemia, or excessive production of blood cells. Looking at a sample of your blood under a microscope can also provide clues to the cause of hemolysis, which is the break down of red blood cells.
Finally, a complete blood count is performed as part of the routine checks, which can help rule out sepsis, a life-threatening infection.
Serum electrolytes –
These are also assessed in order to understand other possible causes for the symptoms. An increase in the potassium level can indicate hemolysis, and changes in the sodium and bicarbonate levels could lead to altered mental status or reveal an overly acidic or alkaline blood condition.
Additional tests –
Lumbar puncture and chest x-ray might also be done to rule out sepsis. Another test that measures bilirubin levels through the skin could also be helpful. In case these results aren’t conclusive, tests to check other substances in your body like ammonia, lactate, heavy metals, and acetaminophen may be done.
Imaging Studies –
Head ultrasound, CT and MRI scans are not typically used for diagnosing kernicterus. They are only done when lab tests don’t provide enough information or are not conclusive. They can however help rule out other causes of brain disfunction.
A special test called a brainstem evoked auditory response (BEAR) is used to check for hearing problems, as it’s common in people with bilirubin toxicity.
Treatment Options for Kernicterus
The main aim of managing kernicterus, a kind of brain damage that happens when a newborn has severe jaundice, is to prevent harm to the brain by reducing bilirubin levels (yellow pigment released during the breakdown of red blood cells). There are three primary methods to prevent and treat high bilirubin levels:
1. Exchange Transfusion Therapy: This is an urgent and effective method to remove already formed bilirubin from the blood. The process involves taking out the infant’s own blood (mainly the plasma) and replacing it with banked blood that does not contain bilirubin. This therapy becomes necessary when there are signs of acute bilirubin brain damage, and when blood levels of bilirubin remain high despite efforts to reduce them. Usually, if bilirubin levels in the blood exceed 20-25 mg/dL, an exchange transfusion is conducted. Keep in mind, though, this procedure carries some infection risks, such as contracting Hepatitis C. It’s also essential to monitor for anomalies, like low blood sugar, low platelet count, high potassium levels, and low calcium levels, that can occur because of the transfusion.
2. Phototherapy: This treatment uses light to change insoluble bilirubin molecules in the body into forms that are soluble in water and can be excreted by the body. During the procedure, the infant’s eyes should be covered to prevent irreversible damage to the retina (light-sensitive layer at the back of the eye). Also, doctors need to monitor for side effects of phototherapy like an inability to control body temperature, tanning, and dehydration. Phototherapy may be initiated when the total bilirubin level in blood is equal to or higher than 15 mg/dL in 1-2 day old infants, 18 mg/dL in 2-3 day old infants, or 20 mg/dL in infants older than 3 days.
3. Intravenous Immunoglobulins (IVIG): IVIG is used when the baby’s jaundice is due to their blood cells being attacked by antibodies in their own blood. This condition can happen when there’s incompatibility between the baby’s and mom’s blood group or Rh factor (a protein on red blood cells). Giving IVIG to newborns with significant hyperbilirubinemia due to such reasons can decrease the need for exchange transfusion without causing immediate negative effects.
Additionally, providing fluid supplementation in full-term babies presenting with severe hyperbilirubinemia can lower the rate of exchange transfusion and the duration of phototherapy.
What else can Kernicterus be?
Neonatal jaundice, or yellowing of a newborn’s skin and eyes, can be caused by many different factors. Newborns are naturally predisposed to jaundice because their bodies are replacing fetal blood cells with adult ones, and their young livers can’t always keep up. But it’s important to remember that normal, or ‘physiologic’, jaundice is a diagnosis made only after other serious conditions have been ruled out. These conditions can result in severe consequences if not addressed. For instance, kernicterus, a type of brain damage from severe jaundice, presents with both jaundice and neurological symptoms, so any diseases that cause these symptoms need to be considered and checked for. Here’s a list of a few conditions to keep in mind:
- Cerebral palsy
- Head trauma
- Neonatal sepsis (an infection in the bloodstream)
- Congenital TORCH infections (a group of infections passed from mother to baby during pregnancy)
- Hypoxic-ischemic brain injury in the newborn (damage caused by lack of oxygen and blood flow)
- Fetal alcohol syndrome (caused by alcohol consumption during pregnancy)
- Cretinism/pediatric hypothyroidism (an underactive thyroid gland)
What to expect with Kernicterus
Kernicterus is a medical condition, and how serious it is depends on how severe the disease is when it’s first found and the treatment it receives. With early detection, and proper treatment immediately provided, the patient can fully recover. Unfortunately, if the diagnosis comes late, it can cause permanent damage to the nervous system. This might lead to uncontrolled movements called chorea, difficulties with sight and hearing, and cerebral palsy (a condition that affects a person’s ability to move and keep their balance and posture).
Kernicterus is a significant health issue in low-middle-income countries, causing 15% of newborn deaths. Therefore, it’s vital to be aware of the symptoms and seek medical help immediately to avoid long-term damage.
Possible Complications When Diagnosed with Kernicterus
Kernicterus, a type of brain damage, can lead to several complications. These complications may include:
- Hearing loss – this is the most common problem
- Motor function issues, such as irregular movements or stiffness (athetosis and chorea)
- Visual problems, like trouble with eye movements (gaze palsies)
- Abnormalities in tooth development
Preventing Kernicterus
When a baby has a risk of developing a condition called kernicterus due to high levels of bilirubin, a substance produced by the body, it becomes extremely important to focus on preventive measures. Kernicterus may lead to neurological problems. Good prenatal care can enable doctors and the expecting mother to be ready for any complications that could make the newborn prone to high levels of bilirubin, or hyperbilirubinemia.
To help with this, the American Academy of Pediatrics (AAP) has shared specific guidelines that link a newborn’s age, in hours, with bilirubin levels. These guidelines also provide advice on managing the situation based on the degree of risk involved. The AAP recommends that all newborn babies have a medical check-up within 48 to 72 hours after birth.
Extra care should be taken with babies who have a family history of high bilirubin levels, were born prematurely, had birth injuries like cephalhematoma (which is a bruise on the baby’s head), or faced other complications. Parents should be taught proper feeding methods and told about the importance of breastfeeding. It’s also crucial for parents to know when to seek medical help. Signs which may indicate an issue include if the baby is less active than usual, seems confused, or has difficulty with their suckling reflex.
